| Rheumatoid arthritis concomitant with depression is rheumatoid arthritis (Rheumatoid arthritis, RA)-induced depression, which belongs to secondary depression type. Its symptoms mainly manifest decreasing interest, retardation of thinking, poor appetite, irritability, despair and even suicide attempts base on the RA symptoms, which severely influence the work, study and life's quality of patients. The pathogenesis of rheumatoid arthritis concomitant with depression remains unclear, recent years, with the development of immunology research, some scholars believe that the pathogenesis of depression may connect with the secretion of cytokines increase, so made "cytokine hypothesis" of depression. The mechanisms of cytokines influence depress-ion preliminarily suggests that cytokines act on the hypothalamus and/or pituitary associated nervous secretion. In this study, we start with immuno-logical view explore the mechanisms of cytokines change, and further reveal the pathogenesis of RA concomitant with depression. Currently, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitor (SSRI), monoamine oxidase inhibitor (MAOI), lithium salt were adopted mainly by western medicine. But these drugs have some shortcomings such as addictive, side effects, expensive, and poor compliance, therefore, clinical application subject to certain restrictions. The TCM clinical effect of RA concomitant with depression was affirmed, which has advantages of less adverse reaction, low price and good patient compliance, just to make up for the lack of western medicine. So, we take theoretical summary and investigation of etiologies, pathogenesis, and syndrome differentiation of RA concomitant with depression from TCM side, meanwhile, we take experimental and clinical observations based on the treatment of our leader teather's proved recipe Bushenhuoxuejieyufang(补肾活血解郁方)Objective:First, we observe the clinical effects of Bushenhuo-xuejieyufang(补肾活血解郁方)RA treating with RA concomitant with depression. Second, the animal model of RA concomitant with depression is established to explore pathogenesis and Chinese medicine intervention of the depression associated with RA. This project providing effective treatment and theory for prevention and therapy of RA concomitant with depression.Methods:First, Clinical part:the principle of randomized, con troll- ed, blind principle is taken,63 patients accord with rheumatoid arthritis, depression, and Chinese medicine syndromes were picked out, the ratio of 1:1 were randomly divided into treatment group and control group, treatment group 32 cases, the control grou-p31 cases. The patients of treatment group on the basis of anti-rheumatic therapy took Bushenhuo-xuejieyufang(补肾活血解郁方)in two services every day. Control group on the basis of conventional anti-rheumatic therapy took fluoxetine hydrochloride for oral, daily doses of 20mg. Each group was treated with oral medication for 6 weeks. After treatment effects were observed. Second, the experimental part:Select female Wistar rats of 32, which are randomly divided into 4 groups, namely the normal group and model group, collagen-induced arthritis group and the depression group, n= 8.Ⅱwith bovine collagen induced arthritis model a week later are given chronic unpredictable mild stress method modeling for a period of 21 days. After modeling, the western medicine treatment group is administered fluoxetine daily, the traditional Chinese medicine treatment group is treated Bushenhuoxuejieyufang recipe for 6 weeks. After modeling and the medicine intervene treatment to respectively evaluate the general of state, behavior evaluation and to detect the cytokines (IL-1β, IL-6, TNF-α) levels.Results:First, Clinical part:(1) comparison of HAMD points:3 weeks after treatment, the treatment group and control group scores significantly higher than pre-treatment. (P<0.01), but the scores between the two groups compared had no significant difference (P>0.05); the treatment group scores than the control group improved slightly at 6 weeks, but the points had no significant difference (P>0.05). After 3 weeks, in treatment group 7 cases had significant improvement,22 cases had progress, 3 cases had no effect, the total effective rate was 90.6%; in control group 9 significant improvement,17 patients had progress,5 patients had no effect, the total effective rate 83.9%; efficacy of two groups had no significant difference (P> 0.05) analyzed by Ridit test, which shows two groups had similar effect. For 6 weeks'treatment, in treatment group, the clinical control was achieved in 6 cases, excellence was 21 cases, and improvent in 22 cases,1 patient had no effect, the total effective rate was 96.9%; in control group, the clinical control was achieved in 23 cases, excellence was 2 cases, improvent in 2 cases, the total effective rate 93.5%; efficacy of two groups had no significant difference (P> 0.05) analyzed by Ridit test, which shows two groups had similar effect. (2) Comparison of TCM Syndrome Scale score:For 3 weeks treatment, TCM symptoms Scale scores of treatment and control group all had improved, which had significant difference (P<0.01); For 6 weeks' treatment, TCM Syndrome Scale scores of treatment and control group had significant difference (P<0.05), which suggested that TCM symptoms of treatment group had better improved condition than control group. For 3 weeks'treatment, in treatment group, the clinical control was achieved in 2 cases, excellence was 22 cases, and improvement in6 cases,2 patients had no effect, the total effective rate was 93.8%; in control group, the clinical control was achieved in 5 cases, improvement in 22 cases,4 patients had no effect, the total effective rate 87.1%; efficacy of two groups had significant difference (P< 0.01) analyzed by Ridit test, which shows treatment group had better improved condition than control group. For 6 weeks'treatment, in treatment group the clinical control was achieved in 2 cases, excellence was 26 cases, and improvement in 1 cases,2 patients had no effect, the total effective rate was 93.8%; in control group, the clinical control was achieved in 1 cases, excellence was 23 cases, improvement in 4 cases,4 patients had no effect, the total effective rate 93.5%; efficacy of two groups had significant difference (P<0.05) analyzed by Ridit test, which shows treatment group had better improved condition than control group. (3) Comparison of rheumatoid arthritis improvement:for 3 weeks treatment, the main symptoms and signs, and physical and chemical indicators of two groups were better than pre-treatment, but no significant statistical differences (P>0.05), which shows two groups had similar effect.for 6 weeks treatment, tender joint count, morning stiffness (min) of the treatment group improved significantly compared with the control group, with significant difference by statistical analysis (P<0.05); compared with the control group, the number of joint swelling, pain levels of treatment group improved significantly, with significant difference by statistical analysis (P<0.01), which showed that after 6 weeks treatment, the improvement of tender joint count, swollen joint count, morning stiffness (min) and level of pain control value of treatment group better than control group. Comparison of efficacy: for 3 weeks' treatment, in treatment group improvement in 1 cases, excellence was 24 cases,7 cases had no effect, the total effective rate was 78.1%; in control group, improvement in 3 cases, excellence was 12 cases,16 cases had no effect, the total effective rate was 48.3%; efficacy of two groups no difference (P>0.05) analyzed by Ridit test, which shows treatment group had better improved condition than control group. The improvement condition of treatment group TCM symptoms had similar effect with control group, for 6 weeks' treatment, in treatment group marked effect was 9 cases, improvement was 17 cases, excellence was 4 case,2 cases had no effect, the total effective rate was 93.8%; in control group, improvement in 19 cases, excellence was 5 cases,3 cases had no effect, the total effective rate was 90.0%; efficacy of two groups had no difference (P>0.05) analyzed by Ridit test, which shows treatment group had better improved condition than control group. The improvement condition of treatment group TCM symptoms had similar effect with control group. (4) during therapy, individual pa:ients had performance of nausea, loss of appetite and mild diarrhea in the treatment group after the drug taken, however, those symptoms disappeared after dosage reduction, in multiple or after meals, and others have no obvious side effects. Second, the experimental part:After model replicating the general condition was observed while behavior and cytokine are determined. model rats had swelling, malformed ankle, arthritis indexes and amount of sugar water drinking increased, the wilderness in the horizontal and vertical test scored significantly less than the normal group, cytokine levels increased, there was a significant difference (P<0.01).After interventional treatment, compared with model group, traditional Chinese medicine and western medicine group general state of rats and behavioral tests improved and significantly decreased cytokine levels, there was significant difference (P<0.01).Conclusions:(1) The treatment of Bushenhuoxuejieyufang(补肾活血解郁方)has similar effect compare to fluoxetine hydrochloride for RA concomitant with depression, while has features of good effect on symptoms, less side effects and good patient compliance. (2) The rat models, beha-vioral testing, histological changes and the indicators of the blood and tissue changes,which accord with the basic disease of collagen-induced arthritis with depression, suggesting that the modeling success. (3) RA concomitant with depression have a close relationship with cytokines, Bushenhuoxuej ieyufang(补肾活血解郁方)can reduce effectively the secre-tion of cytokines to improve the general state and behavior determination results of RA animal model concomitant with depression. |
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